In addition to electrocardiographic stress testing, there are various newer modalities that can be very useful in the determination of disability. However, the physician performing and interpreting such test should have the appropriate training and experience. Stress testing done in conjunction with thallium-201 is a more sensitive tool in the diagnosis of coronary artery disease. Its sensitivity has been reported to range from 68 per cent to 96 per cent (average 84 per cent), compared with a sensitivity of 60 per cent to 70 per cent for exercise ECG alone. The specificity of thallium scintigraphy has been reported to be between 65 per cent and 100 per cent (average 87 per cent), which represents a modest improvement compared with the specificity of exercise ECG alone.
Thallium Scintigraphy
It is often done with SPECT (single photon emission computed tomography) which further increases the sensitivity. However, a stress test with thallium is costly and has the undesirable side effect of exposure to radiation. A total body radiation exposure associated with intravenous injection of 2mCi of thallium-201 is approximately 420 mrad; this amount is equivalent to that of approximately 30 chests X-rays. Thallium scintigraphy, however, is preferable to exercise ECG alone when the resting ECG shows a non-specific abnormality impairing interpretation of exercise ECG alone or when information on the probable reversibility (or nonreversibility) of apparently infarcted segment is needed to estimate the potential value of revascularization therapy. In the majority of cases of disability evaluation, thallium testing is not necessary in determining the disability status, above and beyond what information that can be derived from a standard exercise test.
Some of the illustrated cases of normal and abnormal scanning are shown elsewhere.
Technetium 99M Sestamibi Scan
This study is another form of studying perfusion of the heart. This radioactive study is similar to that of thallium 201. With a combined approach using both thallium and sestamibi 99m, one can decrease the acquisition time by 50 per cent. The information derived from these newer techniques allows for both evaluations of ischaemia and data similar to a first pass MUGA study.This particular technique is more expensive than thallium imaging, but is of shorter time and is useful when information regarding wall motion abnormality and ejection fraction is important as well as the degree and area of ischaemia. This obviates the need for ordering a MUGA scan.
Adenosine or Dipyridamole Thallium Scan
These studies are newer modalities that allow studying perfusion abnormalities to the myocardium when the patient cannot perform a regular treadmill or bike testing. The physician orders one of these studies only if it is important to make an absolute diagnosis of coronary disease and the patient is unable to perform a treadmill test or a bike test. These studies do not mallow for functional disability evaluation but only provide information regarding the presence or absence of myocardial ischaemia.
Stress Echocardiography, with Adenosine, with Dipyridamole, or with Doubtamine These have all been described. The information is that of wall motion abnormality indicating ischaemia. Ejection fraction can also be measured. These techniques are somewhat less expensive than radionuclear studies, but require an experienced technician to obtain a satisfactory study. Pharmacological stress echocardiography is a form of non-exercise stress echocardiography.There are basically two approaches to performing pharmacologic stress with echocardiography.
Potent vasodilators, such as dipyridamole or adenosine produce ischaemia by a “steal phenomenon” whereby blood is shunted away from the obstructed arteries due to dilatation of the normal arteries, thereby producing ischaemia in the area perfused by the obstructed arteries. The alternative approach is to use an adrenergic stimulating drug to simulate exercise. Under these circumstances, ischaemia is produced by increasing the heart rate and blood pressure as with exercise. The most popular pharmacologic agent in this class is Dobutamine. This drug has a strong ionotropic and modest chronotropic effect on the heart.The primary indications for pharmacologic stress are inability to exercise or the desire to identify viable myocardium. Dobutamine infusion to a peak dose of 40 μg/kg/min is the most commonly used pharmacologic stressor, and increases myocardial oxygen consumption through increments in inotropic state, heart rate (usually to 120–140 beats/minute), and blood pressure (by 30–40 mm Hg with peak pressures of 170–180 mm Hg). Serious complications occur in about 3:1000.
Vasodilator agents (adenosine to 0.18 mg/kg/min and dipyridamole to 0.84 mg/kg) are less commonly used for pharmacologic stress echo, and work by the induction of coronary steal,which occurs in the setting of severe or extensive coronary disease. The haemodynamic effects of these stressors are minor, and the most common side effects of dipyridamole and adenosine are headache and dyspnoea, respectively; serious side effects occur in about 1:1000 patients. Atropine may be added if the response to dipyridamole is negative, and other protocols involve combination of dobutamine with a vasodilator.For diagnostic indications, the sensitivity of dobutamine echo is somewhat greater, especially in patients with single vessel disease. From a prognostic angle, a strong evidence base supports both pharmacologic tests. Side effects occur with similar frequency with dipyridamole and dobutamine, although serious problems are more likely with dobutamine. Dobutamine stress is a better choice for those with asthma or untreated conduction system disease, while dipyridamole stress is preferable in patients with serious arrhythmias or severe hypertension.
Imaging Techniques
A screening exam with M-mode and limited Doppler should be performed at the start of the test, but a detailed echo examination is usually not feasible from a logistic standpoint. Stress echo is almost universally performed using transthoracic imaging, usually with harmonic imaging and usually in the two parasternal and three apical views.Digital imaging is very important for stress echo—mostly for side-by-side comparison of regional function at rest and stress, as well as the ability to review the progression of contraction on a frame-by-frame basis which facilitates assessment of the timing of contraction.
Interpretation of Stress Echocardiography
The standard approach to interpretation is qualitative. The attendant need for training and problems posed for reproducibility of the test are the greatest shortcomings of this technique.Visual assessment is based on analysis of thickening (rather than motion, which may be influenced by translation or tethering) before, during, and after stress. A systematic approach to review is essential. On the resting images, global function is assessed by calculation of wall motion score index or ejection fraction, and regional function is evaluated using regional wall motion scoring. Rest and stress images are then compared for the development of global dysfunction (left ventricular enlargement and shape changes) and regional dysfunction. A normal response involves the augmentation of function in all segments. The presence of a new or worsening wall motion abnormality identifies ischaemia, but rather than identifying the test as simply positive, the site, extent, and severity of abnormal function should be identified, as well as the ischaemic threshold if a bicycle or dobutamine stress study is being examined.
Accuracy of Stress Echocardiography
The accuracy of stress echo tests for the detection of coronary artery disease is expressed as the sensitivity and specificity of the technique for the detection of angiographically demonstrated stenoses. In significant studies of exercise echocardiography (> 100 patients), the sensitivity and specificity range from 74–97 per cent and 64–86 per cent, respectively. Higher sensitivity may be
obtained with bicycle exercise (as there is no loss of ischaemia in the post-stress period), but this is at the cost of some impairment in specificity. Comparisons with quantitative angiography have shown stenosis diameters of 0.7–1.0 mm to be associated with ischaemia.Significant studies (> 100 patients) of dobutamine stress echocardiography show a range for sensitivity of between 61–95 per cent, while that for specificity ranged from 51–95 per cent. The addition of atropine augments sensitivity. Dobutamine echocardiography is a more sensitive marker of ischaemia in lesions involving larger (> 2.6 mm diameter) vessels than smaller vessels.
The quantitative angiography parameters associated with ischaemia are a lumen diameter of < 1 mm diameter, per cent diameter stenosis of 52 per cent, and per cent area stenosis of 75 per cent, of which the minimal lumen diameter is most predictive of an abnormal dobutamine stress test.The sensitivity and specificity of dipyridamole and adenosine stress echocardiography for the detection of coronary artery disease range from 61–81per cent and 90–94 per cent, respectively .However, single vessel disease is more difficult to detect using this technique.
Limitations in the Diagnostic use of Stress Echocardiography
Although the presence of coronary artery disease is readily recognised in the setting of multivessel disease, and multivessel pathology is readily recognised in the presence of prior infarction (“ischaemia at a distance”), the technique has a sensitivity of only 50 per cent for the recognition of multivessel disease in normal ventricles. The development of global ventricular dysfunction (reduction of ejection fraction or left ventricular enlargement) should increase the interpreter’s suspicion of multi-vessel disease, although it may reflect loss of contractile reserve in valvar heart disease. Clues to the presence of extensive disease despite apparently localised wall motion abnormalities include the early onset of ischaemia, at a low heart rate and rate–pressure product, or at a low dose of pharmacologic stressor.
The detection of single vessel stenoses may also be problematic, and the sensitivity of stress echo for this problem is probably less than that of myocardial perfusion scintigraphy. Because of problems posed by identification of minor gradations of wall motion in the setting of abnormal function, the identification of ischaemia within areas of resting wall motion abnormalities may be difficult. The problem is probably less during dobutamine stress because ischaemic segments with abnormal resting function often show a biphasic response.
The last three issues reflect fundamental limitations of an ischaemia based technique, which will require either a more sensitive tool for assessment of wall motion, or combination with a perfusion marker such as contrast echocardiography. At present, however, the best way to approach them is to focus on the prognostic, rather than the diagnostic, implications of the test.
Muga Scan
Multi-gated equilibrium radionuclide angiography (MUGA) is a very accurate method in measuring ejection fraction. Rest and exercise equilibrium radionuclide angiography has been used in conjunction with or as an alternative to thallium scintigraphy in the detection of coronary artery disease. Regional or global abnormal wall motion at rest or during exercise can be accurately delineated with this technique. It is also a powerful predictor of subsequent adverse cardiac event. It is also useful in managing patients with stenotic or regurgitant valvular lesions.
It is often done with SPECT (single photon emission computed tomography) which further increases the sensitivity. However, a stress test with thallium is costly and has the undesirable side effect of exposure to radiation. A total body radiation exposure associated with intravenous injection of 2mCi of thallium-201 is approximately 420 mrad; this amount is equivalent to that of approximately 30 chests X-rays. Thallium scintigraphy, however, is preferable to exercise ECG alone when the resting ECG shows a non-specific abnormality impairing interpretation of exercise ECG alone or when information on the probable reversibility (or nonreversibility) of apparently infarcted segment is needed to estimate the potential value of revascularization therapy. In the majority of cases of disability evaluation, thallium testing is not necessary in determining the disability status, above and beyond what information that can be derived from a standard exercise test.
Some of the illustrated cases of normal and abnormal scanning are shown elsewhere.
Technetium 99M Sestamibi Scan
This study is another form of studying perfusion of the heart. This radioactive study is similar to that of thallium 201. With a combined approach using both thallium and sestamibi 99m, one can decrease the acquisition time by 50 per cent. The information derived from these newer techniques allows for both evaluations of ischaemia and data similar to a first pass MUGA study.This particular technique is more expensive than thallium imaging, but is of shorter time and is useful when information regarding wall motion abnormality and ejection fraction is important as well as the degree and area of ischaemia. This obviates the need for ordering a MUGA scan.
Adenosine or Dipyridamole Thallium Scan
These studies are newer modalities that allow studying perfusion abnormalities to the myocardium when the patient cannot perform a regular treadmill or bike testing. The physician orders one of these studies only if it is important to make an absolute diagnosis of coronary disease and the patient is unable to perform a treadmill test or a bike test. These studies do not mallow for functional disability evaluation but only provide information regarding the presence or absence of myocardial ischaemia.
Stress Echocardiography, with Adenosine, with Dipyridamole, or with Doubtamine These have all been described. The information is that of wall motion abnormality indicating ischaemia. Ejection fraction can also be measured. These techniques are somewhat less expensive than radionuclear studies, but require an experienced technician to obtain a satisfactory study. Pharmacological stress echocardiography is a form of non-exercise stress echocardiography.There are basically two approaches to performing pharmacologic stress with echocardiography.
Potent vasodilators, such as dipyridamole or adenosine produce ischaemia by a “steal phenomenon” whereby blood is shunted away from the obstructed arteries due to dilatation of the normal arteries, thereby producing ischaemia in the area perfused by the obstructed arteries. The alternative approach is to use an adrenergic stimulating drug to simulate exercise. Under these circumstances, ischaemia is produced by increasing the heart rate and blood pressure as with exercise. The most popular pharmacologic agent in this class is Dobutamine. This drug has a strong ionotropic and modest chronotropic effect on the heart.The primary indications for pharmacologic stress are inability to exercise or the desire to identify viable myocardium. Dobutamine infusion to a peak dose of 40 μg/kg/min is the most commonly used pharmacologic stressor, and increases myocardial oxygen consumption through increments in inotropic state, heart rate (usually to 120–140 beats/minute), and blood pressure (by 30–40 mm Hg with peak pressures of 170–180 mm Hg). Serious complications occur in about 3:1000.
Vasodilator agents (adenosine to 0.18 mg/kg/min and dipyridamole to 0.84 mg/kg) are less commonly used for pharmacologic stress echo, and work by the induction of coronary steal,which occurs in the setting of severe or extensive coronary disease. The haemodynamic effects of these stressors are minor, and the most common side effects of dipyridamole and adenosine are headache and dyspnoea, respectively; serious side effects occur in about 1:1000 patients. Atropine may be added if the response to dipyridamole is negative, and other protocols involve combination of dobutamine with a vasodilator.For diagnostic indications, the sensitivity of dobutamine echo is somewhat greater, especially in patients with single vessel disease. From a prognostic angle, a strong evidence base supports both pharmacologic tests. Side effects occur with similar frequency with dipyridamole and dobutamine, although serious problems are more likely with dobutamine. Dobutamine stress is a better choice for those with asthma or untreated conduction system disease, while dipyridamole stress is preferable in patients with serious arrhythmias or severe hypertension.
Imaging Techniques
A screening exam with M-mode and limited Doppler should be performed at the start of the test, but a detailed echo examination is usually not feasible from a logistic standpoint. Stress echo is almost universally performed using transthoracic imaging, usually with harmonic imaging and usually in the two parasternal and three apical views.Digital imaging is very important for stress echo—mostly for side-by-side comparison of regional function at rest and stress, as well as the ability to review the progression of contraction on a frame-by-frame basis which facilitates assessment of the timing of contraction.
Interpretation of Stress Echocardiography
The standard approach to interpretation is qualitative. The attendant need for training and problems posed for reproducibility of the test are the greatest shortcomings of this technique.Visual assessment is based on analysis of thickening (rather than motion, which may be influenced by translation or tethering) before, during, and after stress. A systematic approach to review is essential. On the resting images, global function is assessed by calculation of wall motion score index or ejection fraction, and regional function is evaluated using regional wall motion scoring. Rest and stress images are then compared for the development of global dysfunction (left ventricular enlargement and shape changes) and regional dysfunction. A normal response involves the augmentation of function in all segments. The presence of a new or worsening wall motion abnormality identifies ischaemia, but rather than identifying the test as simply positive, the site, extent, and severity of abnormal function should be identified, as well as the ischaemic threshold if a bicycle or dobutamine stress study is being examined.
Accuracy of Stress Echocardiography
The accuracy of stress echo tests for the detection of coronary artery disease is expressed as the sensitivity and specificity of the technique for the detection of angiographically demonstrated stenoses. In significant studies of exercise echocardiography (> 100 patients), the sensitivity and specificity range from 74–97 per cent and 64–86 per cent, respectively. Higher sensitivity may be
obtained with bicycle exercise (as there is no loss of ischaemia in the post-stress period), but this is at the cost of some impairment in specificity. Comparisons with quantitative angiography have shown stenosis diameters of 0.7–1.0 mm to be associated with ischaemia.Significant studies (> 100 patients) of dobutamine stress echocardiography show a range for sensitivity of between 61–95 per cent, while that for specificity ranged from 51–95 per cent. The addition of atropine augments sensitivity. Dobutamine echocardiography is a more sensitive marker of ischaemia in lesions involving larger (> 2.6 mm diameter) vessels than smaller vessels.
The quantitative angiography parameters associated with ischaemia are a lumen diameter of < 1 mm diameter, per cent diameter stenosis of 52 per cent, and per cent area stenosis of 75 per cent, of which the minimal lumen diameter is most predictive of an abnormal dobutamine stress test.The sensitivity and specificity of dipyridamole and adenosine stress echocardiography for the detection of coronary artery disease range from 61–81per cent and 90–94 per cent, respectively .However, single vessel disease is more difficult to detect using this technique.
Limitations in the Diagnostic use of Stress Echocardiography
Although the presence of coronary artery disease is readily recognised in the setting of multivessel disease, and multivessel pathology is readily recognised in the presence of prior infarction (“ischaemia at a distance”), the technique has a sensitivity of only 50 per cent for the recognition of multivessel disease in normal ventricles. The development of global ventricular dysfunction (reduction of ejection fraction or left ventricular enlargement) should increase the interpreter’s suspicion of multi-vessel disease, although it may reflect loss of contractile reserve in valvar heart disease. Clues to the presence of extensive disease despite apparently localised wall motion abnormalities include the early onset of ischaemia, at a low heart rate and rate–pressure product, or at a low dose of pharmacologic stressor.
The detection of single vessel stenoses may also be problematic, and the sensitivity of stress echo for this problem is probably less than that of myocardial perfusion scintigraphy. Because of problems posed by identification of minor gradations of wall motion in the setting of abnormal function, the identification of ischaemia within areas of resting wall motion abnormalities may be difficult. The problem is probably less during dobutamine stress because ischaemic segments with abnormal resting function often show a biphasic response.
The last three issues reflect fundamental limitations of an ischaemia based technique, which will require either a more sensitive tool for assessment of wall motion, or combination with a perfusion marker such as contrast echocardiography. At present, however, the best way to approach them is to focus on the prognostic, rather than the diagnostic, implications of the test.
Muga Scan
Multi-gated equilibrium radionuclide angiography (MUGA) is a very accurate method in measuring ejection fraction. Rest and exercise equilibrium radionuclide angiography has been used in conjunction with or as an alternative to thallium scintigraphy in the detection of coronary artery disease. Regional or global abnormal wall motion at rest or during exercise can be accurately delineated with this technique. It is also a powerful predictor of subsequent adverse cardiac event. It is also useful in managing patients with stenotic or regurgitant valvular lesions.
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